The major objective of this research problem is the chemical and immunological characterization of the dimorphic fungus, Histoplasma capsulatum. The chemical characterization of the antigenic mosaic of these two phases of the organism will contribute information to workers concerned with pathogenicity. Knowledge of the composition of the cell walls of both the yeast-like and filamentous phases is of pertinent interest to cell biologists concerned with the phenomenon of cellular differentiation (dimorphism). Studies on immunologically active culture filtrates (histoplasmins), culture lysates, and purified fractions are being assayed chemically for carbohydrate protein, lipid and nucleic acid composition. The alterations caused by enzymic and chemical treatments during the fractionation of these immunogens are assayed by complement-fixation and immuno-diffusion employing sera from proven human cases of histoplasmosis and sera from infected and immunized animals. Information thus obtained will provide methods for the preparation of specific diagnostic tools for the study of histoplasmosis. Parallel chemical and immunological studies employing mannans, glucans and cell wall fractions of Candida albicans and sera from animals infected with C. albicans have been employed for control purposes. Serologic cross reactivity has been demonstrated with polysaccharide fractions of H. capsulatum when tested with sera from animals infected with C. albicans. It is intended that correlation can be drawn between the serology of experimental infection and those of natural origin.